This is a large multidisciplinary, collaborative program in which the primary objectives of the research are to expand our understanding of the structure, biochemistry and function of normal human embryonic and fetal skin during development, and to determine how the normal properties are altered antenatally by inherited skin disease. Studies are planned in three categories: 1) those in which we will continue to characterize the development of skin (epidermis, dermis and dermal-epidermal junction) in terms of various structural and biochemical markers of differentiation, 2) those which will provide insight into dermal-epidermal interactions that may influence the differentiation of the two tissues and the morphogenesis of the epidermis, and 3) those related to specific clinical studies. Studies in the first category include assays for age-related expression of involucrin, EGF-receptors, cell surface glycoconjugates and type V collagen by epidermal keratinocytes, and of antigens and receptors by Langerhans cells; of type VII collagen correlated with the appearance of anchoring fibrils at the DEJ; and of elastin and GAGs in the dermis. Morphometric studies of the epidermal cell surface are planned to increase our understanding of a possible role of the skin in transport during early gestation. The structure and biochemistry of premature skin will be studied and computer-assisted reconstruction will be used to evaluate the development of nerve/vessel networks of the skin. Cell culture, organ culture, artificial matrix cultures and grafts of fetal skin to the nude will be systems employed to evaluate dermal-epidermal interactions in tissue recombinant experiments. The clinical studies are focused on the evaluation of skin samples obtained at fetos-copy, and from newborns affected with inherited skin disease, studies of adult patients with ectodermal dysplasias; biochemical characterization of "fresh" amniotic fluid cells; studies of healing wounds from fetuses biopsied in utero; and examination of tissue from fetuses and newborns exposed to isotretinoin in utero (Vitmin A teratology). A consortium agreement has been planned to continue studies of lipid expression and biosynthesis (in culture) in embryonic, fetal and premature skin.